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PubMed1995

Enhancement of interleukin-6 production by fibrinogen degradation product D in human peripheral monocytes and perfused murine liver.

The effect of fibrinogen degradation products D and E (FDP-D, FDP-E) on IL-6 production in perfused mouse livers and peripheral monocytes is studied. Similarly to bacterial endotoxin FDP-D is highly potent to augment the IL-6 production measured in perfused mouse livers, while FDP-E is not stimulatory. FDP-D but not FDP-E is able to stimulate the in vitro IL-6 production of human peripheral monocytes, as well. Plasmin alone is almost ineffective on IL-6 production both in perfused livers and monocytes. Our findings suggest a direct positive feedback circuit, among fibrinogen, FDP and IL-6.

Adult↗

PubMed1994

Staphylococcal glycocalyx activates macrophage prostaglandin E2 and interleukin 1 production and modulates tumor necrosis factor alpha and nitric oxide production.

We have examined the effect of staphylococcal glycocalyces on the ability of murine peritoneal macrophages to produce prostaglandin E2 (PGE2) and the inflammatory cytokines interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) and to generate nitric oxide. Glycocalyx partially purified under endotoxin-free conditions from defined liquid medium cultures of Staphylococcus lugdunensis or Staphylococcus epidermidis was a strong stimulator of PGE2 and IL-1 production. The addition of 10 to 100 micrograms of glycocalyx per ml induced levels of IL-1 and PGE2 production similar to that induced by 0.1 to 1 micrograms of Escherichia coli lipopolysaccharide (LPS) per ml. In contrast, glycocalyx induced ninefold less TNF-alpha and three- to fourfold less nitrite than LPS. A modulatory effect was suggested by the observation that the amount of TNF-alpha and nitrite generated remained constant whether the macrophages were stimulated with 10 or 100 micrograms of glycocalyx per ml. A selective modulation of macrophage activation was confirmed by the demonstration that costimulation of macrophages with both glycocalyx and LPS resulted in a reduction in TNF-alpha and nitrite generation relative to stimulation with LPS alone even though costimulation had no effect on PGE2 production and increased IL-1 production. Involvement of PGE2 in this modulatory effect was suggested by the ability of indomethacin to augment glycocalyx-stimulated TNF-alpha production and to reverse the inhibitory effect of glycocalyx on LPS induction of TNF-alpha production. However, the inability of indomethacin to reverse the inhibitory effect of glycocalyx on LPS-induced nitric oxide generation suggests that the selective modulation of macrophage function by glycocalyx may be more complex than increased sensitivity to PGE2 feedback inhibition.

Animals↗

PubMed1986

Secretory activity of the intraocular homotransplanted pars intermedia of the frog, Rana nigromaculata.

To examine whether there is a possible inhibitory effect of melanophore-stimulating hormone (MSH) on the release of MSH from the pars intermedia, two groups of frogs, Rana nigromaculata, were prepared with median eminence extirpation to eliminate the inhibitory hypothalamic control over MSH secretion. In one of the two groups, the animal's own intermediate lobe was transplanted to the anterior chamber of the eye (intraocular autotransplanted gland), and in the second, the animal's own pars intermedia was left in situ, and another pars intermedia was homotransplanted intraocularly. The MSH content of the homotransplanted pars intermedia was usually much increased and the number of secretory granules augmented in the secretory cells in comparison with the autotransplanted gland. These results lead to the conclusion that the release of MSH from the intraocular pars intermedia is inhibited by the in situ pars intermedia of host animals and indicate that MSH acts directly at the pituitary level to inhibit its further release, thus supporting the concept of mass action-type feedback control.

Animals↗

PubMed1980

Effect of slide projections and tape-recorded suggestions on thermal biofeedback training.

A previous experiment (Herzfeld & Taub, 1977) demonstrated that slide projections and explicit suggestions relating to thermal experiences can significantly augment temperature self-regulations training (.5 degrees F, p less than .05). however, the experimental design was thought to result in an underestimate of the magnitude of the effect, since each subject served as his own control and could therefore make use on nonsuggestion training days of material provided on training days. In this experiment, separate groups of subjects either were given feedback combined with the suggestion procedure on each of 8 training days or were given feedback alone. The mean temperature self-regulation of the suggestion group (2.01 degrees F) was significantly better than the self-regulation (.73) of the nonsuggestion group (t test, p less than 0.01), a difference of 1.28 degrees F.

Audiovisual Aids↗

PubMed1993

Changes in extracellular adenosine during chemical or electrical brain stimulation.

The purpose of this study was to determine the changes in adenosine and adenosine metabolites during graded electrical stimulation or kainic acid-induced activation and to assess the role of adenosine in the cerebral blood flow (CBF) response to increased brain activity. A modified brain microdialysis technique was used to sample cerebral interstitial fluid (ISF), deliver drugs locally to the brain, electrically stimulate the brain, and measure local CBF (H2 clearance). Microdialysis probes were implanted bilaterally in the caudate nuclei of ketamine-anesthetized rats. Graded electrical stimulation at 5, 15, and 30 Hz increased dialysate adenosine 1.5-fold, 2.3-fold, and 4.7-fold, respectively. Local infusion of kainic acid, an agonist of the excitatory amino acid neurotransmitter glutamate, produced a transient increase (2-fold) in dialysate adenosine and sustained increases in dialysate inosine (2-fold), hypoxanthine (4-fold) and CBF (2.4-fold). When the adenosine receptor antagonist 8(p-sulphophenyl)-theophylline (SPT, 10(-3) M) was co-administered with kainic acid, CBF increased only 1.6-fold, while the increase in dialysate adenosine was augmented by 40%. These data demonstrate that ISF adenosine increases during brain activation and suggest that adenosine contributes to active hyperemia in the brain.

Adenosine↗

PubMed2003

Brain renin-angiotensin system dysfunction in hypertension: recent advances and perspectives.

This review focuses on the dysfunction of the intrinsic brain renin-angiotensin system (RAS) in the pathogenesis of hypertension. Hyperactivity of the brain RAS plays a critical role in mediating hypertension in both humans and animal models of hypertension, including the spontaneously hypertensive rat (SHR). The specific mechanisms by which increased brain RAS activity results in hypertension are not well understood but include increases in sympathetic vasomotor tone and impaired arterial baroreflex function. We discuss the contribution of endogenous angiotensin (Ang) II actions on presympathetic vasomotor rostral ventrolateral medulla neurons to enhance sympathetic activity and maintain hypertension. In addition, we discuss Ang II-induced attenuation of afferent baroreceptor feedback within the nucleus tractus solitarius and its relevance to the development of hypertension. We also outline the cellular and molecular mechanisms of Ang II signal transduction that may be critical for the initiation and establishment of hypertension. In particular, we present evidence for a phosphoinositide-3-kinase-dependent signaling pathway that appears to contribute to hypertension in the SHR, possibly via augmented Ang II-induced increases in neuronal firing rate and enhanced transcriptional noradrenaline neuromodulation. Finally, we outline future directions in utilizing our understanding of the brain RAS dysfunction in hypertension for the development of improved therapeutic intervention in hypertension.

Angiotensin II↗

PubMed1997

Effect of repeated activin-A treatment on the activity of the hypothalamic-pituitary-gonadal axis of the adult male rat.

The present study was undertaken to determine whether recombinant activin-A increases mRNA levels of the peptide GnRH, and whether this phenomenon correlates with increased FSH and/or LH release. One acute s.c. injection of activin-A (120 micrograms/kg body weight) to adult male rats was found to significantly (P < 0.01) increase plasma FSH levels, with no detectable changes in LH or testosterone (T) release. Similarly, there were no significant differences between GnRH mRNA values measured in the medial preoptic area of the hypothalamus. When activin-A was administered s.c. every 8 h for seven consecutive treatments, similar results were obtained for gonadotropin release; in addition, we observed a significant (p < 0.01) up-regulation of hypothalamic GnRH mRNA levels. The administration of activin-A intracerebroventricularly (i.c.v., 6 micrograms/rat) according to the same chronic schedule also produced a significant (p < 0.01) increase in FSH levels, as well as a modest, but detectable, elevation in LH concentrations, and a large augmentation of T secretion. In contrast, there were no changes in steady-state GnRH mRNA concentrations. Collectively, these results show that both the systemic (s.c.) and the central (i.c.v.) injection of activin-A stimulates FSH secretion. While we had originally thought that the lack of response of hypothalamic GnRH neurons to i.c.v. activin injections might have been due to increased steroid feedback, the observation that comparable results were obtained in both intact and castrated rats does not support this hypothesis. One possibility is that the previously reported stimulatory influence of i.c.v. activin-A treatment on neurons that manufacture corticotropin-releasing factor, and consequently on circulating catecholamine concentrations, may have increased testicular activity independently of changes in pituitary function.

Activins↗

PubMed1973

Some effects of inhibiting endogenous prostaglandin formation on the responses of the cat spleen.

1. Cat isolated spleens release prostaglandins into the venous effluent in response to stimuli such as nerve stimulation, noradrenaline and angiotensin II.2. The release of prostaglandins is abolished by pre-treatment of the spleen with indomethacin (0.3-5 mug/ml).3. The capsular and vascular responses to the different stimuli are augmented after inhibition of prostaglandin release.4. The prevention of prostaglandin release, as well as the augmentation of vascular and capsular responses, are reversible after indomethacin treatment is stopped.5. The role of prostaglandins as modulators of the responses to several stimuli is discussed.

Angiotensin II↗

PubMed1976

Characterization of the inappropriate gonadotropin secretion in polycystic ovary syndrome.

To evaluate gonadotropin release in polycystic ovary syndrome (PCO), one or more of the following hypothalamic-pituitary function tests were performed on 24 patients with the syndrome. These tests included (a) the pulsatile pattern and day-to-day fluctuation of gonadotropin release; (b) effects of exogenous estrogen and antiestrogen (clomiphene) administration on gonadotropin release; and (c) pituitary responsiveness to maximal (150 mug) and submaximal (10 mug) luteinizing hormone-releasing factor (LRF) injections. In 10 of the 14 patients sampled frequently (15 min) for 6 h, luteinizing hormone (LH) levels were elevated above the concentration seen in normal cycling women (except the LH surge). These high LH concentrations appeared to be maintained by and temporally related to the presence of exaggerated pulsatile LH release, either in the form of enhanced amplitude or increased frequency. In all subjects, levels of follicle-stimulating hormone (FSH) were low or low normal, and a pulsatile pattern was not discernible. In four patients, daily sampling revealed marked day-to-day fluctuation of LH but not FSH. That the elevated LH levels were not related to a defect in the negative-feedback effect of estrogen was suggested by the appropriate fall of LH in four patients given an acute intravenous infusion of 17beta-estradiol. This infusion had no effect on FSH levels. In addition, clomiphene elicited rises of both LH and FSH that were comparable to the ones observed in normal women given the same treatment. The clomiphene study also suggested that the positive-feed-back mechanism of estrogen on LH release was intact when the preovulatory rises of 17beta-estradiol induced appropriate LH surges. The elevated LH levels appeared to be related to a heightened pituitary responsiveness to the LRF. This was found in the 11 and 2 patients given maximal (150 mug) and submaximal (10 mug) doses of LRF, respectively. The augmented pituitary sensitivity for LH release correlated with the basal levels of both estrone (P less than 0.025) and 17beta-estradiol (P less than 0.02). The net increase in FSH was significantly greater (P less than 0.001) in the PCO patients than the normal women with maximal doses of LRF. With the smaller dose study none of the injections had a discernible effect on FSH concentrations in either subject. The disparity between LH and FSH secretion could be explained by the preferential inhibitory action of estrogen on FSH release, coupled with a relative insensitivity of FSH release. These data indicate that in these PCO patients the abnormalities of the hypothalamic-pituitary regulation of gonadotropin secretion was not an inherent defect but represented a functional derangement consequent to inappropriate estrogen feedback, which led to a vicious cycle of chronic anovulation and inappropriate gonadotropin secretion.

Adult↗

PubMedDate not supplied

Mechanisms of hypothalamic-pituitary-gonadal disruption in polycystic ovarian syndrome.

Although the pathogenesis of polycystic ovarian syndrome (PCOS) is still controversial, a series of investigations has demonstrated an array of neuroendocrine abnormalities as a major component of the syndrome. From a neuroendocrine perspective, patients with PCOS exhibit an accelerated frequency and/or higher amplitude of LH pulses, augmentation of LH secretory burst mass, and a more disorderly LH release. Elevated in vitro LH bioactivity and a preponderance of basic LH isoforms, which correlate positively with elevated serum 17-hydroxyprogesterone, androstenedione, and testosterone concentrations, also characterize adolescents with PCOS. Heightened GnRH drive of gonadotropin secretion and a steroid-permissive milieu appear to jointly promote elevated secretion of basic LH isoforms. Positive feedback is implied, because hypersecretion of highly bioactive LH in PCOS probably contributes to inordinate androgen output. However, the precise nature of feedback disruption remains uncertain. Indeed, recent data suggest that PCOS is marked by anomalies of both feedforward and feedback signaling between GnRH/LH and ovarian androgens. From a single hormone perspective, the individual patterns of LH and androstenedione release are consistently more irregular in patients with PCOS. Bihormonal analysis has disclosed concomitant uncoupling of the pairwise synchrony of LH and testosterone, LH and androstenedione, and testosterone and androstenedione secretion. The foregoing ensemble of findings points to deterioration of both orderly uniglandular and coordinate bihormonal output in PCOS. Additional studies are needed to establish the primary pathophysiologic mechanisms underlying this disorder.

17-alpha-Hydroxyprogesterone↗

PubMed1984

Pituitary gonadotropin-releasing hormone (GnRH) receptor responses to GnRH in hypothalamus-lesioned rats: inhibition of responses by hyperprolactinemia and evidence that testosterone and estradiol modulate gonadotropin secretion at postreceptor sites.

Increased hypothalamic GnRH secretion appears to influence positively the number of pituitary GnRH receptors (GnRH-R). GnRH-R increase after castration in male rats, and this rise can be prevented by testosterone (T), anti-GnRH sera, or hypothalamic lesions. GnRH also increases serum LH and GnRH-R in hypothalamus-lesioned rats, and these animals injected with exogenous GnRH are, therefore, a good model in which to study the site of steroid feedback at the pituitary level. Adult male and female rats were gonadectomized, and radiofrequency lesions were placed in the hypothalamus. Males received T implants, and females received estradiol implants at the time of surgery. Empty capsules were placed in the control animals. Beginning 3-5 days later, animals in each group were injected every 8 h with vehicle (BSA) or GnRH (0.002-200 micrograms/day) for 2 days. After these GnRH injections, all rats received 6.6 micrograms GnRH, sc, 1 h before decapitation to determine acute LH and FSH responses. GnRH-R were determined by saturation analysis using 125I-D-Ala6-GnRH ethylamide as ligand. In males, GnRH injections increased GnRH-R. T inhibited acute LH and FSH responses to GnRH in all groups, but had little effect on GnRH-R, indicating that T inhibits gonadotropin secretion at a post-GnRH receptor site. In females, the GnRH-R response to GnRH was less marked, and only the 200 micrograms/day dose of GnRH increased GnRH-R, indicating that the positive feedback effects of estradiol at the pituitary level are also exerted at a site distal to the GnRH receptor. There was no positive correlation between the number of GnRH-R and GnRH-stimulated gonadotropin release in males or females. Female rats with hypothalamic lesions had markedly elevated serum PRL levels (greater than 300 ng/ml). Suppression of PRL secretion by bromocryptine resulted in augmented GnRH-R responses to GnRH, and GnRH-R concentrations rose to the same values induced in males. This suggests that hyperprolactinemia inhibits GnRH-R responses to GnRH in females by a direct action on the pituitary gonadotroph.

Animals↗

PubMed2026

Human-AI Interaction With AI-Assisted Tumor Overlays in Pediatric Whole-Body Magnetic Resonance Imaging: Exploratory Reader Study.

BACKGROUND: AI tools have the potential to enhance personalized clinical care, particularly in radiology. However, their integration into clinical workflows remains complex, especially in pediatric oncology, where early cancer detection is critical. Children with Li-Fraumeni syndrome (LFS), a rare cancer predisposition disorder, undergo regular surveillance whole-body magnetic resonance imaging (wbMRI), which presents an opportunity for AI-assisted tumor detection. OBJECTIVE: We evaluated the feasibility of an AI-assisted overlay for highlighting tumor-like regions in pediatric surveillance wbMRI and explored how access to the overlay influenced radiologist workflow, candidate-lesion marking behavior, follow-up recommendations, and perceived workload. METHODS: We developed a patch-based AI segmentation model trained on augmented 2D slices from 675 surveillance wbMRI volumes of pediatric patients with LFS. The model was designed to highlight regions with high tumor probability. A reader study was conducted with 2 radiologists who independently reviewed wbMRI cases both with and without AI assistance. We measured evaluation time, number and location of reader-marked candidate lesions, type of follow-up recommendation, and subjective feedback using structured questionnaires. RESULTS: AI assistance altered interpretation workflows for both radiologists, with mixed effects. On average, the time required to evaluate each case increased when using the AI tool for both radiologists. However, one radiologist had an increase in the number of candidate lesion locations selected with the tool, and one had a decrease in the number of candidate lesion locations selected with the tool. Subjective feedback indicated that one of the radiologists reported lower mental demand with the AI tool, while both radiologists reported lower stress with the AI tool. Interrater variability was evident, underscoring the need for personalized calibration of AI tools. CONCLUSIONS: AI-assisted wbMRI interpretation can improve tumor detection in pediatric cancer surveillance by reducing false negatives. However, its influence on workflow efficiency and interradiologist variability highlights the importance of careful implementation. Successful integration requires addressing challenges such as improving the predictive precision of AI models, offering intuitive end-user designs and instructions, and building trust in AI outputs. AI outputs can influence workflow and behavior in reader-specific ways. Clinical translation will require larger, randomized, multireader studies and model refinement to reduce false positives and quantify lesion-level reader performance. This can help ensure better patient outcomes in addition to reduced clinician burnout.

Humans↗

PubMed1998

Inducible nitric oxide: an autoregulatory feedback inhibitor of vascular inflammation.

Inducible nitric oxide (iNO) is produced at sites of vascular inflammation by resident and nonresident vascular wall cells, but its role in the inflammatory process is not known. In this study, we show that a novel function of iNO is to terminate inflammatory processes. We find that iNO produced by murine macrophage-like cells, RAW264.7, can inhibit cytokine-induced endothelial cell activation in a separated and mixed endothelial-RAW264.7 coculture system. Both iNO production and endothelial VCAM-1 expression were induced simultaneously with bacterial LPS and murine-specific IFN-gamma. Inhibition of iNO synthase (iNOS) activity with N omega-monomethyl-L-arginine in endothelial-RAW264.7 cocultures, stimulated with murine-specific IFN-gamma and LPS, decreased iNO production by 86%, augmented VCAM-1 and iNOS expression in endothelial and RAW264.7 cells, respectively, and increased monocyte adhesion to the endothelial cell surface. Transient transfection studies using various VCAM-1 promoter constructs demonstrated that inhibitory effects of iNO on VCAM-1 gene transcription were mediated, in part, by inhibitory effects of iNO on kappa B cis-acting elements. Immunofluorescence studies using an Ab to the RelA (p65) subunit of nuclear factor-kappa B revealed that iNO inhibited the activation of nuclear factor-kappa B. These studies indicate that iNO attenuates iNOS expression in macrophages and inhibits monocyte adhesion to endothelial cells, and suggest that endogenously derived iNO may be an important autoregulatory inhibitor of vascular inflammation.

Animals↗

PubMed1982

The energy costs of temperature regulation in birds: the influence of quick sinusoidal temperature fluctuations on the gaseous metabolism of the Japanese quail (Coturnix coturnix japonica).

1. Quick sinusoidal temperature fluctuations (constant average 10 degrees C) cause an increase in metabolism in comparison to an invariable constant ambient temperature of the same dimension. 2. At the observed mean value of 10 degrees C metabolism is increased by 0.8% per 1 K/hr based on the values of resting metabolic rate (correlation: M = 53.5 + 0.445 Ta, M in J/K g hr, Ta = ambient temperature change in K/hr) and 0.6% based on the values of activity metabolism (M = 70.4 + 0.425 Ta). 3. The absolute augmentation of metabolism per 1K/hr is, by comparison, the same for day and night. Its amount is 0.42 and 0.43 J/K g hr respectively. 4. In the response of metabolism to temperature fluctuations no differences could be found with respect to the amplitude and frequency modifications of temperature. 5. The increase of energy consumption is probably caused to a greater extent by "overshoot" of the feedback control system in the course of adjusting metabolism to new levels according to the ambient temperature conditions. 6. Short term ambient temperature changes (i.e. measuring different temperature levels in one night to test basic metabolism vs ambient temperature) cannot produce reasonable values for basic metabolic rate, since these artificially high values reflect the testing procedure.

Animals↗

PubMed1986

Preferential stimulation of iododeoxyuridine phosphorylation by 5'-aminothymidine in human bladder cancer cells in vitro.

5'-Aminothymidine represents a novel class of compounds capable of antagonizing the feedback inhibition which normally regulates thymidine kinase. As a consequence, the uptake of iododeoxyuridine, a substrate of thymidine kinase, can be substantially increased by 5'-aminothymidine. in this study the phosphorylation, uptake, and cytotoxicity of iododeoxyuridine was markedly enhanced by 5'-aminothymidine in three human bladder cancer cell lines, T24, HT1197 and 647V. In contrast, neither the uptake nor the toxicity of iododeoxyuridine was increased by 5'-aminothymidine in normal human urothelial cells propagated in vitro. Although 30 microM 5'-aminothymidine increased the uptake of 3 microM iododeoxyuridine 4- to 5-fold in the HT1197 and 647V cells and 2.5-fold in the T24 cells, no stimulation was produced in the normal urothelial cells. The modulation of iododeoxyuridine uptake was associated with parallel changes in the inhibition of cellular replication. The cytotoxicity of iododeoxyuridine was strongly augmented by 5'-aminothymidine in the HT1197 and 647V cells, modestly increased in the T24 cells, and unchanged in the normal urothelial cells. The degree to which iododeoxyuridine phosphorylation was stimulated did not correlate with cellular replication rates or with intracellular thymidine triphosphate concentrations. Iododeoxyuridine uptake was markedly increased in the HT1197 (doubling time = 52 h) and 647V (doubling time = 24 h) cells, moderately in the rapidly growing cells T24 (doubling time = 20 h), and minimally in the normal urothelial cells which doubled every 32 h. In exponentially growing cells the thymidine triphosphate pools were approximately 18 microM in the normal cells and about 21, 24, and 35 microM in the HT1197, T24, and 647V cells, respectively. The use of 5'-aminothymidine and other compounds capable of antagonizing feedback inhibition may provide a new means of increasing the efficacy of cytotoxic nucleosides.

Antimetabolites, Antineoplastic↗

PubMed1977

The effects of testosterone and its 5alpha-reduced metabolites on pituitary responsiveness to gonadotrophin-releasing hormone (Gn-RH).

The aim of this study was to investigate effects of androgens on gonadotrophin release in response to gonadotrophin-releasing hormone (Gn-RH) stimulation in vitro. Hemipituitaries of mature male rats were pre-incubated for 90 min with T, DHT, 3alpha- or 3beta-diol (4 ng or 4 microgram/ml medium), and the incubation continued for 240 min after adding Gn-RH (1 ng/ml medium). Gn-RH caused a 4-5-fold rise in the secretion of LH and a 2-fold rise in FSH secretion. The effect of the androgens was dose-dependent. At low levels, T and DHT exerted no effect on Gn-RH-stimulated gonadotrophin release, whereas the two androstanediols (3alpha- and 3beta-diol) augmented the Gn-RH stimulation of both gonadotrophins, though preferentially LH. With high doses of androgens, the results obtained showed: a) no effect of T; b) DHT suppression of the Gn-RH-stimulated FSH release; c) suppression of Gn-RH stimulation by 3alpha- and 3beta-diol regarding both LH and FSH. It is concluded that T exerts through its reduced metabolites a feedback effect on the pituitary gland responsiveness to Gn-RH stimulation.

Androstane-3,17-diol↗

PubMed1995

The preovulatory gonadotrophin-releasing hormone surge: a neuroendocrine signal for ovulation.

Recent studies have demonstrated that an important component of the positive feedback response to oestradiol in mammals is an action within the central nervous system to induce a large surge in the secretion of gonadotrophin-releasing hormone (GnRH). This oestradiol-induced neuroendocrine signal for ovulation has been best characterized in ewes. The GnRH surge is high in amplitude; the amount secreted increases on average more than 40 times above the pre-surge baseline value. The initial increment in GnRH secretion precedes or coincides with the onset of the LH surge. The GnRH surge is of extended duration, lasting far longer than the preovulatory LH surge. A molecular variant of GnRH, which is less active biologically than native GnRH, is co-secreted at the time of the surge, but termination of the LH surge cannot be accounted for by a change in biological activity of the secreted GnRH. Generation of the GnRH surge appears to follow a characteristic progressive change in the pattern of GnRH in portal blood. High concentrations of oestradiol initially stimulate the secretion of GnRH between pulses; this is followed by augmentation of both pulsatile and interpulse GnRH release producing the rising limb of the surge. Finally, recent experiments have indicated that the local application of oestradiol to the ventromedial nucleus of the hypothalamus is sufficient to stimulate the GnRH surge, suggesting a key rol for this hypothalamic area in the generation of this neuroendocrine signal for ovulation.

Animals↗

PubMed1976

Effects of lesions in the parabrachial nucleus on the mechanisms for central and reflex termination of inspiration in the cat.

The effects of PCO2 and body temperature on the time course and peak amplitude of the central inspiratory activity (CIA) and the inspiratory "off-switch" threshold was studied in apneustic and non-apneustic cats. Apneusis resulted from lesions of the inspiratory inhibiting structures of the medial parabrachial nucleus (NPBM) and by interrupting vagal volume feedback. The cats were paralyzed and ventilated either proportionally to their phrenic output or at predetermined rate and volume. The dependence of the rate of rise and maximal amplitude of phrenic activity on PCO2 and body temperature were comparable in apneustic and non-lesioned animals. The Hering-Breuer volume threshold for inspiratory termination was increased following the rostral pontine lesions. Both hyperthermia and hypercapnia caused augmentation of the absolute rate of rise of inspiratory activity but hypercapnia, in contrast to hyperthermia, caused virtually no change in the fractional increment per unit time. With hypercapnia the inspiratory "off-switch" threshold was raised in the apneustic animals in intact ones, whereas hyperthermia did not seem to influence this threshold. In apneustic conditions expiratory duration remained constant, independent of the large variations in the inspiratory durations. Our results suggest that the NPBM merely provides an excitatory, threshold-lowering input to the inspiratory "off-switch" mechanism.

Animals↗